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Pediatric Annals May 2023Adolescence marks a period of significant neural maturation and development of lifelong habits, including the potential use of recreational psychostimulant drugs....
Adolescence marks a period of significant neural maturation and development of lifelong habits, including the potential use of recreational psychostimulant drugs. Increased prevalence of drug adulteration and fatalities related to drug overdose pose new challenges for individuals who use drugs recreationally. As the prevalence of recreational psychostimulant use drastically increases during young adulthood, pediatric and adolescent health care providers can play a crucial role in the lifelong well-being of their patients by identifying those with risk factors for consequences associated with substance use at an early age. This article discusses the epidemiology, pharmacology, clinical manifestations, complications, and common methods of use for three types of psychostimulant drugs-amphetamines, methamphetamine, and 3,4-Methylenedioxymethamphetamine. This article aims to provide pediatric and adolescent health care providers with practical knowledge to effectively perform substance use screening, brief intervention, and referral to treatment with the goal of reducing drug-related morbidity and mortality among the adolescent age group. .
Topics: Humans; Adolescent; Child; Young Adult; Adult; Central Nervous System Stimulants; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Illicit Drugs; Referral and Consultation
PubMed: 37159061
DOI: 10.3928/19382359-20230307-05 -
Psychopharmacology Feb 2018The use of (±)-3,4-methylenedioxymethamphetamine ((±)-MDMA) as an adjunct to psychotherapy in the treatment of psychiatric and behavioral disorders dates back over... (Review)
Review
The use of (±)-3,4-methylenedioxymethamphetamine ((±)-MDMA) as an adjunct to psychotherapy in the treatment of psychiatric and behavioral disorders dates back over 50 years. Only in recent years have controlled and peer-reviewed preclinical and clinical studies lent support to (±)-MDMA's hypothesized clinical utility. However, the clinical utility of (±)-MDMA is potentially mitigated by a range of demonstrated adverse effects. One potential solution could lie in the individual S(+) and R(-) enantiomers that comprise (±)-MDMA. Individual enantiomers of racemic compounds have been employed in psychiatry to improve a drug's therapeutic index. Although no research has explored the individual effects of either S(+)-MDMA or R(-)-MDMA in humans in a controlled manner, preclinical research has examined similarities and differences between the two molecules and the racemic compound. This review addresses information related to the pharmacodynamics, neurotoxicity, physiological effects, and behavioral effects of S(+)-MDMA and R(-)-MDMA that might guide preclinical and clinical research. The current preclinical evidence suggests that R(-)-MDMA may provide an improved therapeutic index, maintaining the therapeutic effects of (±)-MDMA with a reduced side effect profile, and that future investigations should investigate the therapeutic potential of R(-)-MDMA.
Topics: Animals; Hallucinogens; Humans; Mental Disorders; N-Methyl-3,4-methylenedioxyamphetamine; Stereoisomerism; Stress, Psychological
PubMed: 29248945
DOI: 10.1007/s00213-017-4812-5 -
Neuroscience and Biobehavioral Reviews Nov 2023Functional magnetic resonance imaging (fMRI) is increasingly used to non-invasively study the acute impact of psychedelics on the human brain. While fMRI is a promising... (Review)
Review
Functional magnetic resonance imaging (fMRI) is increasingly used to non-invasively study the acute impact of psychedelics on the human brain. While fMRI is a promising tool for measuring brain function in response to psychedelics, it also has known methodological challenges. We conducted a systematic review of fMRI studies examining acute responses to experimentally administered psychedelics in order to identify convergent findings and characterize heterogeneity in the literature. We reviewed 91 full-text papers; these studies were notable for substantial heterogeneity in design, task, dosage, drug timing, and statistical approach. Data recycling was common, with 51 unique samples across 91 studies. Fifty-seven studies (54%) did not meet contemporary standards for Type I error correction or control of motion artifact. Psilocybin and LSD were consistently reported to moderate the connectivity architecture of the sensorimotor-association cortical axis. Studies also consistently reported that ketamine administration increased activation in the dorsomedial prefrontal cortex. Moving forward, use of best practices such as pre-registration, standardized image processing and statistical testing, and data sharing will be important in this rapidly developing field.
Topics: Humans; Hallucinogens; Ketamine; N-Methyl-3,4-methylenedioxyamphetamine; Psilocybin; Brain
PubMed: 37802267
DOI: 10.1016/j.neubiorev.2023.105421 -
Journal of Psychopharmacology (Oxford,... Dec 2023Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) frequently co-occur in patients who have experienced trauma. This comorbidity leads to a vicious... (Review)
Review
Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) frequently co-occur in patients who have experienced trauma. This comorbidity leads to a vicious cycle where PTSD symptoms beget heavy drinking and vice versa. There are no FDA-approved medications to treat PTSD-AUD; therefore, individuals suffering from this comorbidity are treated with medication approved to treat the disorders separately or with off-label pharmacological interventions. However, these medications are limited in their efficacy for treating PTSD-AUD comorbidity. Emerging research on the nonclassical psychedelic drug 3,4-methylenedioxymethamphetamine (MDMA) suggests that it may be an effective drug used in conjunction with psychotherapy. The following reviews the current research for clinical pharmacotherapies, as well as MDMA-integrative psychotherapy as they pertain to PTSD and AUD in isolation and co-occurrence. Future directions for the role of psychedelic-integrative therapy for the treatment of this comorbidity are discussed.
Topics: Humans; N-Methyl-3,4-methylenedioxyamphetamine; Alcoholism; Stress Disorders, Post-Traumatic; Hallucinogens; Psychotherapy; Comorbidity
PubMed: 38009477
DOI: 10.1177/02698811231200880 -
Psychopharmacology Mar 2022±3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug that shows substantial promise as a psychotherapeutic agent. Still, there is some concern regarding its... (Review)
Review
RATIONALE
±3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug that shows substantial promise as a psychotherapeutic agent. Still, there is some concern regarding its behavioral toxicity, and its dose-effect relationship is poorly understood. We previously explored the role of dose in the cognitive effects of MDMA in a systematic review of existing literature and found no evidence in animals that MDMA impairs memory at low doses (< 3 mg/kg) but mixed results at high doses (≥ 3 mg/kg). Since this review comprised mostly of single-dose studies and an assortment of methodologies, an empirical dose-ranging study on this topic is warranted.
OBJECTIVES
The current study aims to evaluate the conclusion from our systematic review that 3 mg/kg may be the threshold for MDMA-induced amnesia, and to further understand the dose-effect relationship of MDMA on behavioral assays of memory, addiction, and depression.
METHODS
We systematically examined the effects of 0.01 to 10 mg/kg MDMA on Pavlovian fear conditioning; behavioral sensitization, conditioned place preference, and conditioned responding; and the Porsolt forced swim test in mice.
RESULTS
High doses of MDMA (≥ 3 mg/kg) produced amnesia of fear conditioning memory, some evidence of an addictive potential, and antidepressant effects, while low doses of MDMA (≤ 1 mg/kg) had no effect on these behaviors.
CONCLUSIONS
The present dose-ranging study provides further evidence that 3 mg/kg is the threshold for MDMA-induced amnesia. These findings, in addition to our systematic review, demonstrate that careful selection of MDMA dose is critical. High doses (≥ 3 mg/kg) should likely be avoided due to evidence that they can produce amnesia and addiction. Conversely, there is little evidence to suggest that low doses, which are usually administered in clinical studies (approximately 1-2 mg/kg), will lead to these same adverse effects. Ultra-low doses (< 1 mg/kg) are likely even safer and should be investigated for therapeutic effects in future studies.
Topics: Amnesia; Animals; Conditioning, Classical; Depression; Dose-Response Relationship, Drug; Fear; Mice; N-Methyl-3,4-methylenedioxyamphetamine
PubMed: 35179622
DOI: 10.1007/s00213-022-06086-9 -
Experimental Neurology Jan 20223,4 Methylenedioxymethamphetamine generally referred to as MDMA or 'ecstasy' is a ring-substituted phenethylamine stimulant which produces powerful empathogenic effects.... (Review)
Review
3,4 Methylenedioxymethamphetamine generally referred to as MDMA or 'ecstasy' is a ring-substituted phenethylamine stimulant which produces powerful empathogenic effects. Use of MDMA remains popular despite prohibition, and potential long-term negative consequences of repeated use. MDMA produces its acute subjective effects primarily by stimulating the release of serotonin via action at the serotonin transporter (SERT). There is evidence that MDMA administration may lead to long lasting neurotoxic effects on serotonin neurons in primates, and reductions in markers of central serotonin axons, and axon terminals in animals. In humans, demonstration of serotonergic neurotoxicity is much more difficult to identify, and much of the research is complicated by confounding issues of polysubstance use, genetic and environmental factors and reliance on self-reports of previous drug use. We do not review the mechanisms for neurotoxicity in detail as they are covered elsewhere in this special issue. There is a large body of literature, however, which has investigated potential cognitive and neurocognitive consequences of repeated MDMA use. Here we review the literature on cognition, and neuroimaging studies that have investigated structural and functional brain changes associated with ecstasy use.
Topics: Brain; Cognition; Hallucinogens; Humans; N-Methyl-3,4-methylenedioxyamphetamine
PubMed: 34624331
DOI: 10.1016/j.expneurol.2021.113888 -
Psychopharmacology Mar 2022Prospective memory (PM) impairment in recreational drug users has been documented in recent years. However, most studies on the effects of drugs on PM contain several...
Prospective memory (PM) impairment in recreational drug users has been documented in recent years. However, most studies on the effects of drugs on PM contain several methodological challenges, such as small sample size (< 100 participants), unrepresentative sample type (e.g., student or patient), short abstinence period (< 7 days), and lack of control of potential confounds (e.g., sleep and IQ). The present study investigated the possible consequences of recreational drug use on prospective memory, using self-report and lab-based prospective memory measures while overcoming the methodological challenges. The sample was composed of 47 non-users (27 females, age range from 18 to 50 +) and 53 drug users (21 females, age range from 18 to 50 +). Recreational drug users reported significantly more deficits in the long-term episodic, short-term habitual, and internally cued PM failures subscales of the Prospective Memory Questionnaire. However, these deficits were eliminated after controlling for covariates (e.g., age, sleep quality, general health, alcohol usage). Recreational drug users also performed worse than non-users in the short-term, long-term, event-based, and time-based PM subscales of the Royal Prince Alfred Prospective Memory Test. These results remained significant after controlling for the covariates. Drug users demonstrated greater impairments on time-based and long-term PM tasks thought to be linked with executive functioning. Taken together, the present study provides further support for recreational drug-related deficits in PM and highlights a dissociation between self-report and lab-based PM measures.
Topics: Female; Humans; Memory Disorders; Memory, Episodic; N-Methyl-3,4-methylenedioxyamphetamine; Neuropsychological Tests; Recreational Drug Use; Substance-Related Disorders
PubMed: 35129670
DOI: 10.1007/s00213-022-06081-0 -
Neuropharmacology Nov 2018Alcohol use disorder represents a serious clinical, social and personal burden on its sufferers and a significant financial strain on society. Current treatments, both... (Review)
Review
Alcohol use disorder represents a serious clinical, social and personal burden on its sufferers and a significant financial strain on society. Current treatments, both psychological and pharmacological are poor, with high rates of relapse after medical detoxification and dedicated treatment programs. The earliest historical roots of psychedelic drug-assisted psychotherapy in the 1950s were associated with Lysergic acid diethylamide (LSD)-assisted psychotherapy to treat what was then called, alcoholism. But results were varied and psychedelic therapy with LSD and other 'classical' psychedelics fell out of favour in the wake of socio-political pressures and cultural changes. A current revisiting of psychedelic clinical research is now targeting substance use disorders - and particularly alcohol use disorder - again. 3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy has never been formally explored as a treatment for any form of substance use disorder. But in recent years MDMA has risen in prominence as an agent to treat posttraumatic stress disorder (PTSD). With its unique receptor profile and a relatively well-tolerated subjective experience of drug effects when used clinically, MDMA Therapy is ideally suited to allow a patient to explore and address painful memories without being overwhelmed by negative affect. Given that alcohol use disorder is so often associated with early traumatic experiences, the author is proposing in a current on-going UK-based study that patients with alcohol use disorder who have undergone a medical detoxification from alcohol might benefit from a course of MDMA-assisted psychotherapy. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.
Topics: Alcoholism; Combined Modality Therapy; Hallucinogens; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Psychotherapy
PubMed: 29126911
DOI: 10.1016/j.neuropharm.2017.11.004 -
Nature Sep 2022
Topics: Humans; Brain; Hallucinogens; N-Methyl-3,4-methylenedioxyamphetamine
PubMed: 36171365
DOI: 10.1038/d41586-022-02871-w -
The Australian and New Zealand Journal... Jul 2023
Topics: Humans; Psilocybin; N-Methyl-3,4-methylenedioxyamphetamine; Hallucinogens; Mental Disorders
PubMed: 37161273
DOI: 10.1177/00048674231174171